S-Nitrosated biodegradable polymers for biomedical applications: synthesis, characterization and impact of thiol structure on the physicochemical properties

Abstract

A new class of nitric oxide (NO)-releasing biodegradable polymers has been synthesized by derivatizing poly(lactic-co-glycolic-co-hydroxymethyl propionic acid) (PLGH) polymers with structurally unique thiol functionalities followed by nitrosation with t-butyl nitrite to yield pendant S-nitrosothiol moieties. The extent of thiolation was found to be dependent on the thiol moiety itself with the efficiency of incorporation as follows: cysteamine > cysteine > homocysteine. Glutathione and penicillamine were not incorporated to any significant extent. The structure and polymer environment associated with the pendant thiol has been related to the physicochemical properties of the resulting polymers. To quantify the extent of S-nitrosation, chemiluminescence and UV-visible spectroscopy techniques were employed in combination. The cysteamine and homocysteine derivatives were found to have the highest extent of nitrosation at 93 ± 3% and 96 ± 3%, respectively, followed by 43 ± 1% for cysteine. Thermal decomposition led to near-complete recovery of NO based upon the quantification of the RSNO formation for each nitrosated polymer. Our ability to exert control over the thiol structure, extent of incorporation and the subsequent nitrosation is crucial to the resulting range of NO release kinetics that were yielded. The functional utility of these materials is demonstrated in that these non-toxic polymers release NO under physiological conditions, have degradation profiles that are appropriate for tissue scaffolds and can be prepared as electrospun nanofibers, commonly used in tissue and bone regeneration applications.